title: Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites.
abstract: BACKGROUND
  Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction.
  
  
  RESULTS
  Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65) and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68). Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10), while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]).
  
  
  CONCLUSIONS
  Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used. Please see later in the article for the Editors' Summary.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America ; National Center for Emerging and Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Feikin
authors.forename: Eunice W
authors.initials: EW
authors.lastname: Kagucia
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Loo
authors.forename: Ruth
authors.initials: R
authors.lastname: Link-Gelles
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.forename: Thomas
authors.initials: T
authors.lastname: Cherian
authors.forename: Orin S
authors.initials: OS
authors.lastname: Levine
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Whitney
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D019992:Databases as Topic; D006287:Health Planning Guidelines; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000517:prevention & control; D015201:Meta-Analysis as Topic; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011159:Population Surveillance; D012703:Serotyping; D055815:Young Adult
chemical_list: D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines